Evins 2014

Methods	Country: USA Setting: Massachussetts General Hospital and 9 other community mental health centres in Massachussetts, Michigan, New Hampshire, Indiana, Alabama, Minnesota Aim: To determine whether smokers diagnosed with schizophrenia and bipolar disease have higher rates of prolonged tobacco abstinence with maintenance pharmacotherapy than with standard treatment Study Design: Double‐blind placebo‐controlled RCT Dates conducted: March 2008 ‐ April 2012 Analysis: "The study was powered to show differences between varenicline and placebo for point‐prevalence abstinence at week 52. Assuming a 35% to 40% relapse in the varenicline group and a 75% to 80% relapse in the placebo group, estimates based on trials of bupropion involving smokers with schizophrenia, we estimated that 48 participants per study group would provide 91% to 99% power and 40 patients per study group would provide 85% to 98% power to detect a treatment effect using a 2‐group Fisher exact test with a .05, 2‐sided significance level"
Participants	247 outpatient smokers with schizophrenia, schizoaffective or bipolar disorder, aged 18 ‐ 70, CPD 10+, 87 of whom met the abstinence criteria after 12 wks of open‐label varenicline to enter this relapse prevention trial. Randomised to varenicline (40) or control (47). Mean age 48, 37% women, 74% white, mean FTND 5.9, mean CPD 23.2
Interventions	All participants had received 12 wks open‐label varenicline, and were confirmed abstinent at wks 11 and 12 1. Varenicline 1 mg x 2/day for a further 40 wks, + tapered CBT relapse prevention counselling 2. Placebo, same regimen, i.e. CBT alone
Outcomes	Primary: 7‐day PPA at wk 52 (12 wks cessation treatment + 40 weeks relapse prevention treatment); Secondary: PPA and CAR at wk 64 (52 wks after achieving abstinence); effect of varenicline on psychiatric symptoms (Calgary Depression Scale for Schizophrenia, Brief Psychiatric Rating Scale, Schedule for Assessment of Negative Symptoms), nicotine withdrawal symptoms (Wisconsin SmokingWithdrawal Scale), health‐related quality of life (SF‐12), body mass index, and adverse events Validation: CO < 9 ppm
Treatment type	Medication: VARENICLINE
Notes	New for 2016 update Funding: NIDA grant R01 DA021245, DHHS grant 05B1MACMHS, Pfizer
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Randomization was conducted via centralized computer‐generated random sequence performed by Massachusetts General Hospital research pharmacy staff members, who were not otherwise involved in the trial, in double‐blind fashion, in blocks of 4, stratified by study site and by a single categorical predictor that was a combination of psychiatric disorder and type of antipsychotic medication (eMethods 1 in the Supplement), using a permuted block design with 1:1 ratio"
Allocation concealment (selection bias)	Low risk	See above
Blinding (performance bias and detection bias) All outcomes	Low risk	See above. "participants were followed up for biochemically verified abstinence and safety outcomes under double‐blind conditions through week 64"
Incomplete outcome data (attrition bias) All outcomes	Low risk	Losses fully reported; by wk 52, 33/40 varenicline participants completed study, and 28/42 placebo participants. ITT analyses conducted
Selective reporting (reporting bias)	Low risk	None noted
Other bias	Low risk	"Telephone follow‐up at week 76 for self report of smoking behavior from those who had achieved continuous abstinence from weeks 12 through 64 was added to the protocol after trial commencement to better evaluate the duration of continuous abstinence after discontinuation of maintenance treatment."